0274 Associations of TNFα Gene Polymorphism with Resilience to Sleep Deprivation and Caffeine Sensitivity

Abstract

Abstract Introduction Sleep deprivation degrades the fidelity of human brain information processing, leading to cognitive impairment. Carriers of the A allele of a single nucleotide polymorphism of the TNFα gene (G308A, rs1800629) have been found to be resilient to cognitive impairment due to sleep deprivation as compared to individuals homozygous for the G allele. Caffeine mitigates the cognitive impairment associated with sleep deprivation. We investigated whether the effects of caffeine and TNFα genotype interact. Methods In an 18-day, controlled, in-laboratory study, 12 healthy adults (age 27.4±6.9; 6 females) underwent three sessions of 48-hour total sleep deprivation (TSD), with each TSD session preceded and followed by three nights of baseline and/or recovery sleep (10 hours time in bed). In randomized, counterbalanced, double-blind, placebo-controlled fashion, during each TSD session a specific dose of caffeine (0, 200, or 300 mg) was administered four times at 12-hour intervals. Vigilant attention was measured every 2 hours during each TSD session with a psychomotor vigilance test (PVT), for which the log of the signal-to-noise ratio (LSNR) derived from the RT distribution was determined as a measure of the fidelity of information processing. Each subject’s TNFα genotype was assessed from a blood sample. Results Subjects homozygous for the TNFα G allele showed greater PVT impairment during sleep deprivation in the 0 mg caffeine (i.e., placebo) condition as compared to carriers of the A allele and as compared to the 200 and 300 mg caffeine conditions (mixed-effects ANOVA, genotype by dose interaction: F2,566=5.23, p=0.005). There was no appreciable caffeine-related difference in performance for carriers of the A allele, who were relatively resilient to TSD regardless of caffeine dose. Conclusion These results suggest non-additive, interacting effects of TNFα genotype and caffeine and a potentially shared mechanism of action with regard to the fidelity of information processing during sleep deprivation. Support This research was supported by ONR. AJB, TJB, VFC, RHR were supported by DoD MOMRP-USAMRDC. The views expressed here are those of the authors and do not represent the official policy or position of the DoD.